应用门控心肌显像定量分析室壁局部运动对心功能的影响

目的 利用定量门控^99mTc-MIBI心肌显像评价左心室室壁各节段运动对左心功能的影响。 方法 对768例患者进行门控^99mTc-MIBI心肌显像,采用QGSPECT程序定量获得20节段的局部室壁运动(WM)及左心室射血分数(LVEF)值。分析LVEF与心室各节段WM的关系。 结果 所得4个公共因子分别代表不同的节段信息,F₁反映了心尖、侧壁的近心尖和中段、前壁、下壁和下间隔的近心尖的信息。F₂反映了前壁和下间隔的中段、整个前间隔的信息。F₃反映了前壁和下侧壁的基底段的信息。F₄反映了下壁的中段和基底段及下间隔基底段的信息。利用多元线性回归分析的方法得出其对LVEF影响的大小顺序为F₁＞F₃＞F₂＞F₄(标准回归系数分别为0.633、0.471、0.415、0.169,P＜0.001)。 结论 应用定量门控心肌显像获得的WM与LVEF有显著的相关性,影响最大的包括心尖、侧壁的近心尖和中段、前壁、下壁和下间隔的近心尖。     

定量门控99Tcm-甲氧基异丁基异腈心肌显像评价局部室壁运动的可靠性

目的与二维超声心动图检查结果比较,探讨定量门控99Tcm-甲氧基异丁基异腈(MIBI)心肌显像评价局部室壁运动的可靠性.方法研究对象为1997-10/2000-09暨南大学医学院第一附属医院核医学科接受门控99Tcm-MIBI心肌显像和二维超声心动图检查的不同左室功能的受试者.对158例不同左室功能受试者进行门控99Tcm-MIBI心肌显像,采用QGSPECT程序评价左室总体和各区域局部室壁运动.并与静态二维超声心动图进行比较.结果左室总体局部室壁运动定量门控99Tcm-MIBI心肌显像评价室壁运动与超声心动图的结果基本符合(观察符合率88.3%,Kappa=0.63,P<0.01).左室各区域局部室壁运动定量门控99Tcm-MIBI心肌显像能较准确评价左室前壁、前侧壁、后侧壁、下壁、前间壁、后间壁和后壁局部室壁运动(观察符合率分别为94.9%,92.0%,96.2%,93.0%,81.0%,77.2%,86.7%,81.0%,Kappa=0.46～0.74,P<0.01).结论定量门控99Tcm-MIBI心肌显像能较准确评价室壁运动,为患者心功能预后评价提供临床依据.     

定量门控^99Tc^m—甲氧基异丁基异腈心肌显像评价局部室壁运动的可靠性

目的：与二维超声心动图检查结果比较，探讨定量门控^99Tc^m—甲氧基异丁基异腈(MIBI)心肌显像评价局部室壁运动的可靠性。方法：研究对象为1997—10／2000—09暨南大学医学院第一附属医院核医学科接受门控^99Tc^m—MIBI心肌显像和二维超声心动图检查的不同左室功能的受试者。对158例不同左室功能受试者进行门控^99Tc^m—MIBI心肌显像，采用QGSPECT程序评价左室总体和各区域局部室壁运动。并与静态二维超声心动图进行比较。结果：左室总体局部室壁运动：定量门控^99Tc^m—MIBI心肌显像评价室壁运动与超声心动图的结果基本符合(观察符合率88．3％，Kappa=0．63，P&;lt;0．01)。左室各区域局部室壁运动：定量门控^99Tc^m—MIBI心肌显像能较准确评价左室前壁、前侧壁、后侧壁、下壁、前间壁、后间壁和后壁局部室壁运动(观察符合率分别为94．9％，92．0％，96．2％，93．0％，81．0％，77．2％，86．7％，81．0％，Kappa=0．46～0．74，P&;lt;0．01)。结论：定量门控^99Tc^m—MIBI心肌显像能较准确评价室壁运动，为患者心功能预后评价提供临床依据。     

门控心肌显像与心血池显像测量左室射血分数的比较

目的评价ECToolbox软件测量门控心肌显像左室射血分数(LVEF)的临床价值.方法 31例患者接受静息态门控心肌显像,用ECToolbox软件测量LVEF,并与一周内门控心血池显像测量的结果比较.结果全部患者用ECToolbox软件测量值与心血池显像测量值的相关性为r=0.699(P<0.001);二者无统计学差别(P＞0.05).EDV<70 ml组患者ECToolbox软件测量值与心血池显像测量值无相关性;前者高于后者(P<0.05).EDV≥70 ml组ECToolbox软件测量值与心血池显像测量值呈强相关(r=0.834,P<0.001);二者无统计学差别(P＞0.05).ECToolbox软件测量值对左室收缩功能是否正常的判断与门控心血池显像无差别(P＞0.05).结论用门控心肌显像ECToolbox软件测量LVEF与门控心血池显像比较相关性好且结果准确,但EDV<70 ml时会高估测量值.     

利用腺苷负荷门控心肌显像的心功能参数指标评价陈旧性心肌梗死患者的心功能

目的探讨利用腺苷负荷门控心肌灌注显像的心功能参数评价陈旧性心肌梗死(OMI)患者心功能和预后的价值。方法OMI组16例,正常对照组18例,两组均进行99m锝标记甲氧基异丁基异腈(99Tcm-MIBI)腺苷负荷门控灌注显像,分析对比两组间的左室射血分数(LVEF)、舒张末期容积(EDV)、收缩末期容积(ESV)及左室壁运动情况。结果OMI组的LVEF(57.00±23.42)%低于正常对照组(76.44±11.68)%,而左室容积参数EDV明显大于正常对照组(133.00±87.96)ml vs(67.11±19.21)ml和ESV(73.97±83.15)ml vs(17.17±11.36)ml;三维心室运动图像观察发现9例(56.3%)OMI患者出现室壁运动减弱;两组间心功能参数经统计学分析差异均有统计学意义(均P<0.05)。结论腺苷负荷门控心肌灌注显像中测得的功能参数是评价左室功能的重要指标,其对陈旧性心肌梗死患者的心功能评价、疗效观察及预后判定均有重要意义。     

心肌血流灌注与室壁运动在评价冠状动脉疾病中的应用

目的　评价心肌血流灌注与室壁运动 (WM )对预测冠状动脉疾病 (CAD)的应用价值。方法　用间歇二次谐波脉冲反转显像技术 ,对 48例经冠状动脉造影证实的CAD患者行静脉心肌声学造影(MCE)。采用 16节段划分法 ,进行目测半定量心肌造影计分 (MCS) :回声均匀性增强 ,显影时间≤ 90s为1分 ;回声低淡不均匀 ,显影延时 (>90s)为 0 .5分 ;充盈缺损为 0分。室壁运动计分 (WMS) :运动正常、减弱、无运动及矛盾运动分别为 1、2、3、4分。结果　MCE、WM和两者联合应用预测CAD均具有高度的敏感性、特异性和准确性。MCE的敏感性和准确性均高于WM (均 P <0 .0 5)。联合应用MCE和WM的敏感性显著高于WM(P <0 .0 0 1) ,准确性也高于WM (P <0 .0 5) ,与MCE相比敏感性和准确性差异无显著性意义 (均P >0 .0 5)。 3种方法具有类似的特异性 (均P >0 .0 5)。MCS与WMS的等级相关r =-0 .58,P <0 .0 0 1。两者的符合率为 78%。结论　MCE、WM和两者联合应用预测CAD均具有高度的敏感性、特异性和准确性。MCE和MCE +WM预测CAD比WM更敏感和准确。局部心肌血流灌注与室壁运动有较好的符合率 ,且两者的异常程度也有一定的相关性 ,因此MCE WM相匹配的室壁节段比不匹配的节段更能反映是否存在冠状动脉狭窄     

不稳定型心绞痛患者全球急性冠状动脉事件注册评分与心肌灌注显像危险分层的相关研究

目的：研究不稳定型心绞痛患者^99mTc-甲氧基异丁基异腈（MIBI）负荷／静息门控心肌灌注显像危险度分层与全球急性冠状动脉事件注册（GRACE）评分的相关性。方法：2006年6月--2007年11月确诊为不稳定型心绞痛的住院患者37例。首先依据GRACE评分方法进行评分；然后行^99mTc-MIBI运动或腺苷负荷门控心肌灌注显像和静息心肌灌注显像，依据负荷／静息门控心肌灌注显像所测定的可逆性心肌缺血计分值（SDS）和负荷后左室射血分数（LVEF）将患者分为低危组和中危组。分析^99mTc-MIBI负荷／静息门控心肌灌注显像危险分层与GRACE评分的相关性。结果：37例患者均顺利完成^99mTc-MIBI运动或腺苷负荷门控心肌灌注显像和静息心肌灌注显像。低危组和中危组之间的GRACE评分有显著差异（P〈0．01）。GRACE评分与负荷状态下心肌缺血计分值（SSS）呈正相关（r=0．561，P〈0．01），与SDS呈正相关（r=0．623，P〈0．01），与静息状态下心肌缺血计分值（SRS）无关（r=0．175，P〉0．05）。结论：GRACE评分对不稳定型心绞痛患者的核素心肌灌注显像危险度分层有一定的预测价值。     

门控心肌灌注显像室壁运动及室壁增厚率在鉴别前壁稀疏缺损中的价值

目的 评价门控心肌灌注显像（G-MPI）、室壁运动及室壁增厚率对前壁放射性稀疏缺损鉴别诊断的价值。方法以4种不同的方法来诊断前壁阳性：A心肌血流灌注图像阳性；B心肌血流灌注图像阳性且室壁运动阳性；C心肌血流灌注图像阳性且室壁增厚率阳性；D心肌血流灌注图像、室壁运动及室壁增厚率均阳性。以冠状动脉造影结果为标准，比较4种方法判断前壁稀疏缺损的准确性。结果4种方法判断前壁可逆性稀疏缺损的准确性分别为79．2％、91．7％、95．8％、100％，B、C与A差异无显著性，D与A差异有显著性；4种方法判断前壁固定性稀疏缺损的准确性分别为32．0％、80．0％、88．0％、92．0％，B、C、D与A差异均有显著性。结论G-MPI、室壁运动及室壁增厚率检测可提高前壁稀疏缺损的诊断准确性。     

ECToolbox软件计算左心室射血分数的适用性

目的 评价ECToolbox软件中R0、R1、R2公式计算门控心肌灌注显像左心室射血分数(LVEF)的适用性.方法 64例患者[冠状动脉粥样硬化性心脏病(CHD)44例;高血压病20例]接受静息态门控心肌灌注显像(~(99m)Tc-MIBI)和平衡法门控心血池显像(~(99m)Tc-RBC),用ECToolbox软件中的R0、R1、R2公式分别计算LVEF,称为R0 LVEF、R1 LVEF、R2 LVEF.将三种公式的计算结果与平衡法门控心血池显像计算结果对比分析.结果 R0、R1、R2公式LVEF值与门控心血池显像LVEF值均有相关性(r=0.905、0.905、0.903,P均<0.05);χ~2检验三种公式LVEF值落入门控心血池显像LVEF值±15%准确率分别为54.30%、71.40%、22.90%,±30%的准确率为81.40%、88.60%、74.30%;Wilcoxon配对检验结果示R1公式计算结果与门控心血池显像计算结果差异无统计学意义,R0、R2公式计算结果与门控心血池显像计算结果差异有统计学意义.结论 门控心肌灌注显像用ECToolbox软件计算CHD和高血压患者的LVEF时,R1公式最为适用.     

核素显像评价自体骨髓单个核细胞移植治疗心肌梗死后心力衰竭

目的 核素显像观察经冠状动脉自体骨髓单个核细胞移植治疗后心肌梗死心力衰竭患者的心肌血流灌注及心功能的变化,研究自体骨髓单个核细胞移植对于心肌修复和心功能的影响.方法 24例前壁心肌梗死合并心力衰竭的患者,非随机法(患者意愿)分为两组.细胞移植组(BM-MNCs组)10例,经冠状动脉骨髓细胞注射+介入治疗+标准药物治疗;对照组14人,介入治疗+标准药物治疗.所有患者分别于移植术前、术后12个月行超声心动、心肌灌注静息显像及平衡法门控心室显像.结果 术后12个月BM-MNCs组心肌血流灌注评分明显改善(46.67±3.44 vs 29.00±4.50,P=0.0015),对照组较术前无明显改变(46.33±2.80 vs 47.00±4.12,P>0.05),两组间差异具有统计学意义(29.00±4.50 vs 47.00±4.12,P=0.0157).BM-MNCs组心肌梗死区面积明显减少[(38.00±3.86)% vs (29.44±4.73)%,P=0.0009],对照组术后无显著变化[(32.70±5.02)% vs (30.30±4.92)%],两组间的变化无统计学意义.门控心血池显像结果示:移植组术后12个月LVEF值可见轻度升高,但是差异无统计学意义,结果与超声心动图一致.结论 核素心肌显像对心肌梗死后心力衰竭患者BM-MNCs移植后的疗效判断有重要价值,自体骨髓单个核细胞移植后,心肌梗死区域血流灌注得到了明显的改善,心功能得到一定的提高.     

Comparison between segmental wall motion and wall thickening in patients with coronary artery disease using quantitative gated SPECT software

This study was performed to evaluate regional wall motion (WM) and wall thickening (WT) using gated myocardial perfusion single photon emission computed tomography (SPECT) and to determine their similarity and disparity in patients with coronary artery disease (CAD). A total of 44 patients underwent 1 day stress/rest (MIBI) gated SPECT. Commercially available quantitative analysis of gated SPECT (QGS) software was used to generate 3D surface display and cine-mode SPECT display. Left ventricle was divided into nine segments to score WM and WT from 0 (no abnormality) to 4 (severe abnormality) by six independent observers. Finally a mean score was calculated for each segment from the scores of six observers. There was fairly good correlation between WM and WT of individual segments (r = 0.62, p < 0.0001). Concordance rate (|WM ? WT|≤1) was 85%. A large difference between WM and WT (WM ? WT≥2) was observed in 15 segments, including 12 segments with greater WM abnormalities and 3 segments with greater WT abnormalities (lateral and inferior walls). Greater WM abnormalities were most commonly observed in anteroseptal segments especially in post coronary artery bypass grafting (CABG) patients. In conclusion, WM and WT showed similarity on QGS studies. However, these two parameters may be determined separately in gated SPECT studies for comprehensive and robust evaluation of the functional status of myocardium. Analyses based on WM assessment alone may lead to erroneous results especially in septal regions.     

In response to the article by M.B. Imran, K. Morita, I. Adachi, M. Konno, N. Kubo, T. Mochizuki, C. Katoh, T. Kohya, A. Kitabatake, E. Tsukamoto & N. Tamaki Comparison between segmental wall motion and wall thickening in patients with coronary artery disease using quantitative gated SPECT software

This study was performed to evaluate regional wall motion (WM) and wall thickening (WT) using gated myocardial perfusion single photon emission computed tomography (SPECT) and to determine their similarity and disparity in patients with coronary artery disease. A total of 44 patients underwent 1 day stress/rest (MIBI) gated SPECT. Commercially available quantitative analysis of gated SPECT (QGS) software was used to generate 3D surface display and cine-mode SPECT display. Left ventricle was divided into nine segments to score WM and WT from 0 (no abnormality) to 4 (severe abnormality) by six independent observers. Finally a mean score was calculated for each segment from the scores of six observers. There was fairly good correlation between WM and WT of individual segments (r = 0.62, p < 0.0001). Concordance rate (|WM ? WT| ≤ 1) was 85%. A large difference between WM and WT (WM ? WT ≥ 2) was observed in 15 segments, including 12 segments with greater WM abnormalities and 3 segments with greater WT abnormalities (lateral and inferior walls). Greater WM abnormalities were most commonly observed in anteroseptal segments especially in post coronary artery bypass grafting patients. In conclusion, WM and WT showed similarity on QGS studies. However, these two parameters may be determined separately in gated SPECT studies for comprehensive and robust evaluation of the functional status of myocardium. Analyses based on WM assessment alone may lead to erroneous results especially in septal regions.     

Good correlation between gated single photon emission computed myocardial tomography and contrast ventriculography in the assessment of global and regional left ventricular function

Purpose: The purpose of this study was to determine the reliability of the measured left ventricular ejection fraction (LVEF) and wall motion analysis by the recently introduced quantitative electrocardiographically (ECG)-gated myocardial perfusion single-photon emission computed myocardial tomography technique (gated SPECT) (QGS). Materials and methods: We compared technetium-99 m tetrofosmin gated SPECT imaging and contrast ventriculography in the assessment of global and regional left ventricular function in 74 patients with undiagnosed chest pain of whom 27 sustained a previous myocardial infarction. Results: Linear regression analysis demonstrated that gated SPECT determined LVEF correlated well with LVEF determined from contrast ventriculography (y = 0.95x + 1.9, r ² = 0.84, p < 0.0001). Bland–Altman plot analysis showed no systematic difference between the two sets of values derived from the two imaging approaches over a wide range of LVEF values. Exact agreement of segmental wall motion scores was 460 of 518 (89%) segments with a kappa value of 0.76 (p < 0.0001). Conclusion: We conclude that gated SPECT imaging is an accurate and reliable clinical tool to accurately measure global and regional left ventricular function.     

SPECT/CT心肌灌注显像图像配准情况及其对图像质量的影响

目的 探讨SPECT/CT心肌灌注显像CT与SPECT图像的配准及配准不良对CT衰减校正（CTAC）图像质量的影响。方法 分析110例⁹⁹Tc^m-甲氧基异丁基异腈SPECT/CT心肌灌注显像受检者资料,利用仪器自带的图像融合软件观察CT和SPECT图像的配准情况,并对出现配准不良的受检者图像行重新配准。利用靶心图获得左心室各壁的放射性计数百分比,比较不同方向配准不良与重新配准后左心室各壁放射性计数的差异和图像差异。结果 有58例（58/110,52.73%）共出现78次图像配准不良,以x轴方向向右偏移和z轴方向向下偏移最常见。对配准不良的图像重新配准后,前壁、心尖部和侧壁的放射性计数百分比明显增加（t=7.931、2.385、8.320,P均<0.05）,其中x轴方向的配准不良对侧壁的影响最为显著,z轴方向的配准不良对前壁的影响最为显著。图像重新配准后可明显改善左心室前壁、心尖部和侧壁的放射性分布。结论 图像配准不良以x轴方向向右偏移和z轴方向向下偏移最为常见,对前壁、心尖部和侧壁的影响最为显著;对CT和SPECT图像行重新配准后可明显改善左心室各壁的图像质量。     

CT coronary angiography of chronic total occlusions of the coronary arteries: how to recognize and evaluate and usefulness for planning percutaneous coronary interventions

Purpose This investigation sought to determine which newly available asynchrony parameter derived from gated myocardial perfusion SPECT (GMPS) systolic wall thickening data best distinguishes patients with left bundle branch block (LBBB) from normal subjects. Methods and materials Emory Cardiac Toolbox (ECTb) algorithms were used to compute left ventricular (LV) global and regional function and perfusion indices with regional contraction phases for 20 patients with LBBB, and in 9 control (CTL) subjects who had no function or perfusion abnormalities. Histogram plots of phase frequencies versus R–R interval times included phase standard deviation (SD), bandwidth (BW), skewness and kurtosis. Z-score asynchrony measures were derived for phases sampled using the conventional 17-segment model. Results In CTLs contraction occurred nearly simultaneously in all segments, while LBBBs exhibited a wide variety of heterogeneous contraction patterns. Global parameters that differed between LBBBs versus CTLs included EF, end-systolic volume and end-diastolic volume, and asynchrony measures that were different included BW, phase SD and z-scores. Z-scores most strongly discriminated LBBBs from CTLs (93% of cases correctly predicted, logistic regression χ² = 29.7, P < 0.0001). Z-scores, phase SD and lateral–septal wall timing were highly reproducible (r = 0.99, 0.99 and r = 0.87, respectively), with no significant inter-observer differences. Conclusion While traditional global function parameters were different in LBBBs and CTLs, asynchrony parameters characterized LBBB most strongly.     

XStrainTM技术评价尿毒症患者左心室局部与整体收缩功能

目的 探讨XStrain^TM技术测定尿毒症心肌病患者左心室局部与整体收缩功能的可行性。方法 将28例尿毒症患者分两组,A组左心室非肥厚12例,B组左心室肥厚16例;C组为正常对照16名。经胸超声心动图采集并存储3个心动周期心尖四腔心、两腔心及三腔心切面二维灰阶图像。采用XStrain^TM定量软件进行脱机分析,获得收缩期左心室壁16节段纵向/横向应变及应变率,对16节段应变参数取平均值获得整体纵向/横向应变数据,并对以上参数进行统计学分析。结果 16节段心肌收缩期纵向应变及应变率(除中间段后间隔外)、横向应变(除中间段前间壁和后间壁外)、横向应变率为C组>A组>B组(P均<0.05)。尿毒症患者左心室收缩期整体纵向及横向应变较C组明显减低(P<0.05)。结论 XStrain^TM技术可清晰显示左心室心肌,评估左心室收缩功能,可用于定量评估尿毒症心肌病患者左心室局部与整体收缩功能。     

超声联合血清Tg、SPECT/CT诊断分化型甲状腺癌术后颈部淋巴结转移

目的 探讨高频超声结合血清甲状腺球蛋白（Tg）、SPECT/CT诊断分化型甲状腺癌（DTC）术后颈淋巴结转移的价值。方法 收集185例经手术病理证实的 DTC患者,于¹³¹I治疗前常规行甲状腺床区及颈部淋巴结超声扫查,并检查血清Tg;¹³¹I治疗1周后行¹³¹I全身扫描,SPECT颈部断层与同机CT图像融合;结合各项检查、淋巴结穿刺活检及临床随访等确定转移淋巴结。结果 共确诊60例DTC颈部转移,其中超声发现转移淋巴结41例（41/60,68.33%）,SPECT/CT发现45例（45/60,75.00%）,血清Tg阳性25例（25/60,41.67%）。超声与SPECT/CT对颈部淋巴结转移的检出率差异无统计学意义（P>0.05）,与血清Tg差异有统计学意义（P<0.01）。超声诊断颈淋巴结转移符合率为78.92%（146/185）,SPECT/CT诊断符合率为82.70%（153/185）,超声联合血清Tg及SPECT/CT的诊断符合率为88.11%（163/185）。结论 超声对于诊断DTC术后颈淋巴结转移有重要价值,结合血清TG、SPECT/CT有助提高颈淋巴结转移检出率。     

99Tcm-TRODAT-1多巴胺转运蛋白SPECT脑显像在亚临床期和临床期帕金森病模型猴诊断中的研究

目的探讨99Tcm-TRODAT-1多巴胺转运蛋白SPECT脑显像在帕金森病亚临床期诊断中的价值.方法对4只食蟹猴静脉注射多巴胺转运蛋白显像剂99Tcm-TRODAT-1,观察99Tcm-TRODAT-1在不同时间点正常猴体内分布并进行纹状体DAT功能分析.用MPTP分别制备无症状亚临床期和临床期PD猴模型,利用计算机感兴趣区(ROI)技术进行纹状体DAT功能半定量分析.结果99Tcm-TRODAT-1最佳SPECT脑显像时间为注射99Tcm-TRODAT-1后3～4 h.PD猴毁损侧(右侧)纹状体在亚临床期就已存在DAT功能的降低,并随着损伤的加重毁损侧纹状体DAT功能进一步降低,对侧纹状体的DAT也受损.结论99Tcm-TRODAT-1 SPECT脑显像可用于PD的亚临床期诊断和病情监测.     

Effects of pacing rates on global and regional myocardial blood flow

Background: Information is scarce on the effects of right ventricular apical (RVA) pacing on regional and global myocardial blood flow (MBF). The purpose of this study was to assess the relationship between pacing rate and both regional and global MBF. Methods: Four patients with exclusive atrial pacing and six patients with exclusive RVA pacing underwent three consecutive H₂¹⁵O positron emission tomography scans at 60, 90, and 130 pulses per minute (ppm). For each pacing rate, regional and global MBF was determined. In all patients, the left ventricular (LV) function was normal. Results: By varying the atrial pacing rate from 60 to 130 ppm, the mean global MBF increased from 0.94 to 1.40 mL/g/min, whereas the mean septal to lateral MBF ratio decreased from 1.09 to 0.83. In ventricular‐paced patients at corresponding rates, the mean global MBF also increased from 1.07 to 1.52 mL/g/min but here the mean septal to lateral MBF ratio increased from 0.83 to 1.0. Conclusions: During both acute atrial and RVA pacing, regional and global MBF increases with higher pacing rates. However, the septal to lateral MBF ratio decreases with atrial pacing and increases with RVA pacing in patients with normal LV function. In RVA pacing, these different rate‐dependent effects on regional MBF can be considered as a favorable factor that helps to understand why in some long‐term paced patients, LV function is preserved. (PACE 2011; 34:587–592)